To characterize the time course of intramuscular botulinum toxin-induced paresis, we serially performed electrophysiological measurements and recorded the sonographic size of an extensor digitorum brevis (EDB) muscle in 10 human subjects before and after injecting the EDB with 10 units of botulinum-A toxin. All EDB CMAPs decreased within 48 h, with peak decline at day 21 (8.3 +/- 3.1 mV to 3.0 +/- 0.9 mV). Decline of mean rectified voltage during maximal voluntary contraction of the EDB paralleled the change in CMAP amplitude. Average decrements to 2-Hz repetitive stimulation never exceeded 6% (day 42) and exercise failed to facilitate significantly CMAP amplitude. Atrophy peaked at day 42. The F-wave to M-wave ratio increased at day 2; silent periods did not change. Our findings confirm a primary peripheral action of the toxin, but a superimposed, transient central effect of the drug cannot be excluded. Intramuscular injections into EDB provide a useful model for studying chemodenervation effects.